Journal of Antivirals & Antiretrovirals
Open Access

Non-viral Vectors

Non-viral vectors can be loosely grouped as plasmid DNA, liposome-DNA complexes (lipoplexes), and polymer-DNA complexes (polyplexes). Oligonucleotides and their analogues, either alone or in complexes, are also an example of non-viral vector-mediated gene transfer. A substantial number of the human cardiovascular gene therapy protocols are based on plasmid-mediated gene transfer. Although myocardial plasmid-mediated gene transfer is relatively inefficient, it has been the vector system upon which several therapeutic angiogenesis trials have been based. In this setting, transient secretion of antigenic factors by a modest number of gene-modified cells is sufficient for the desired phenotypic effect. Inefficient gene transfer and transient gene expression would not, however, be effective for other muscle-based cardiac pathophysiology’s, the majority of which demand widespread and sustained transgene expression.

The use of synthetic oligonucleotides to modulate gene expression in biological systems has immense research and therapeutic potential. Therapeutic oligonucleotides take multiple forms that include antisense molecules, transcription factor decoys, catalytic oligonucleotides and chimeroplasts. The therapeutic potential of each of these has been explored in cardiovascular disease models and examples of these are given in the subsequent text. In addition to the generic limitations of non-viral vectors, oligonucleotides are also constrained by the problems of short biological half-life and non-specific binding to unintended sequences.